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. 2020 Nov 15;26(22):5934-5942.
doi: 10.1158/1078-0432.CCR-20-2255. Epub 2020 Sep 8.

Multimodal CEA-Targeted Image-Guided Colorectal Cancer Surgery using 111In-Labeled SGM-101

Jan Marie de Gooyer  1   2 , Fortuné M K Elekonawo  3   2 , Desirée L Bos  3 , Rachel S van der Post  4 , André Pèlegrin  5 , Bérénice Framery  6 , Françoise Cailler  6 , Alexander L Vahrmeijer  7 , Johannes H W de Wilt  2 , Mark Rijpkema  3
Affiliations

Multimodal CEA-Targeted Image-Guided Colorectal Cancer Surgery using 111In-Labeled SGM-101

Jan Marie de Gooyer et al. Clin Cancer Res. .

Abstract

Purpose: Intraoperative image guidance may aid in clinical decision-making during surgical treatment of colorectal cancer. We developed the dual-labeled carcinoembryonic antigen-targeting tracer, [111In]In-DTPA-SGM-101, for pre- and intraoperative imaging of colorectal cancer. Subsequently, we investigated the tracer in preclinical biodistribution and multimodal image-guided surgery studies, and assessed the clinical feasibility on patient-derived colorectal cancer samples, paving the way for rapid clinical translation.

Experimental design: SGM-101 was conjugated with p-isothiocyanatobenzyl-diethylenetriaminepentaacetic acid (DTPA) and labeled with Indium-111 (111In). The biodistribution of 3, 10, 30, and 100 μg [111In]In-DTPA-SGM-101 was assessed in a dose escalation study in BALB/c nude mice with subcutaneous LS174T human colonic tumors, followed by a study to determine the optimal timepoint for imaging. Mice with intraperitoneal LS174T tumors underwent micro-SPECT/CT imaging and fluorescence image-guided resection. In a final translational experiment, we incubated freshly resected human tumor specimens with the tracer and assessed the tumor-to-adjacent tissue ratio of both signals.

Results: The optimal protein dose of [111In]In-DTPA-SGM-101 was 30 μg (tumor-to-blood ratio, 5.8 ± 1.1) and the optimal timepoint for imaging was 72 hours after injection (tumor-to-blood ratio, 5.1 ± 1.0). In mice with intraperitoneal tumors, [111In]In-DTPA-SGM-101 enabled preoperative SPECT/CT imaging and fluorescence image-guided resection. After incubation of human tumor samples, overall fluorescence and radiosignal intensities were higher in tumor areas compared with adjacent nontumor tissue (P < 0.001).

Conclusions: [111In]In-DTPA-SGM-101 showed specific accumulation in colorectal tumors, and enabled micro-SPECT/CT imaging and fluorescence image-guided tumor resection. Thus, [111In]In-DTPA-SGM-101 could be a valuable tool for preoperative SPECT/CT imaging and intraoperative radio-guided localization and fluorescence image-guided resection of colorectal cancer.

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